Abstract
Despite the availability of highly efficacious vaccines, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lacks effective drug treatment, which results in a high rate of mortality. To address this therapeutic shortcoming, we applied a systems biology approach to the study of patients hospitalized with severe COVID. We show that, at the time of hospital admission, patients who were equivalent on the clinical ordinal scale displayed significant differential monocyte epigenetic and transcriptomic attributes between those who would survive and those who would succumb to COVID-19. We identified messenger RNA metabolism, RNA splicing, and interferon signaling pathways as key host responses overactivated by patients who would not survive. Those pathways are prime drug targets to reduce mortality of critically ill patients with COVID-19, leading us to identify tacrolimus, zotatifin, and nintedanib as three strong candidates for treatment of severely ill patients at the time of hospital admission.
【초록키워드】 COVID-19, Treatment, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Mortality, Vaccines, interferon, Systems biology, host response, severe acute respiratory syndrome Coronavirus, metabolism, monocyte, COVID, Critically ill, therapeutic, Patient, pathway, drug target, interferon signaling, Hospital admission, RNA splicing, drug treatment, Epigenetic, critically ill patients, tacrolimus, Ordinal Scale, Pathways, Nintedanib, Critically ill patient, Messenger RNA, acute respiratory syndrome, acute respiratory syndrome coronavirus, candidate, severely ill patients, attribute, transcriptomic, Zotatifin, approach, effective, reduce mortality, identify, lack, caused, applied, patients hospitalized, severely ill patient, with COVID-19, 【제목키워드】 Systems biology, approach, reduce mortality, identify, candidate drug, severely ill patient, with COVID-19,